title: Age sensitivity of NFκB abundance and programmed cell death in erythrocytes induced by NFκB inhibitors.
abstract: OBJECTIVE
  Erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte outer membrane. Susceptibility to eryptosis is enhanced in aged erythrocytes and stimulated by NFκB-inhibitors Bay 11-7082 and parthenolide. Here we explored whether expression of NFκB and susceptibility to inhibitor-induced eryptosis is sensitive to erythrocyte age.
  
  
  METHODS
  Human erythrocytes were separated into five fractions, based on age-associated characteristics cell density and volume. NFκB compared to ß-actin protein abundance was estimated by Western blotting and cell volume from forward scatter. Phosphatidylserine exposure was identified using annexin-V binding.
  
  
  RESULTS
  NFκB was most abundant in young erythrocytes but virtually absent in aged erythrocytes. A 24h or 48h exposure to Ringer resulted in spontaneous decrease of forward scatter and increase of annexin V binding, effects more pronounced in aged than in young erythrocytes. Both, Bay 11-7082 (20 µM) and parthenolide (100 µM) triggered eryptosis, effects again most pronounced in aged erythrocytes.
  
  
  CONCLUSIONS
  NFκB protein abundance is lowest and spontaneous eryptosis as well as susceptibility to Bay 11-7082 and parthenolide highest in aged erythrocytes. Thus, inhibition of NFκB signalling alone is not responsible for the stimulation of eryptosis by parthenolide or Bay 11-7082.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Ghashghaeinia
authors.forename: Judith C
authors.initials: JC
authors.lastname: Cluitmans
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Toulany
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saki
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lang
authors.forename: Peter
authors.initials: P
authors.lastname: Dreischer
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Michael
authors.initials: M
authors.lastname: Duszenko
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Giel J
authors.initials: GJ
authors.lastname: Bosman
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
mesh_terms: D000375:Aging / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D016328:NF-kappa B; D009570:Nitriles; D012717:Sesquiterpenes; D013450:Sulfones; C002669:parthenolide